HIV-associated immune suppression contributes to increased colonization of commensal and opportunistic pathogens in the mouth, leading to oral complications in many HIV-infected patients. With the increasing number of HIV cases and longer life-expectancy of HIV patients, HIV-associated periodontal disease is expanding as a major health care issue. We hypothesize that HIV infection of tissue resident macrophages contribute directly to this compromise in oralpharyngeal immunity and enhanced host sensitivity to periodontal pathogens, such as the anaerobic bacterium Porphyromonas gingivalis. We are proposing to employ tissue resident macrophages from the oral cavity, specifically palatine tonsils, as a tractable primary cell model to study how HIV impacts macrophage function and associated oral pathogenesis. In addition, we propose determining signals that lead to epigenetic regulation in the context of the primary macrophages. An important aspect of this proposal is our ability to access clinical samples from patients with HIV and our previous experience in providing them with dental care. Using this cohort and our collective expertise, we will perform studies that complement our in vitro studies by characterizing macrophages and cytokines that are present in the oral cavities of HIV infected and control individuals. Upon completion of these studies, we expect to have novel insights into how PD infections contribute to a microenvironment that facilitates HIV replication, inflammation and further periodontal tissue destruction, directly contributing to HIV-associated oral pathogenesis.